Age-associated decrease of type IIA/B human skeletal muscle fibers.

Elderly individuals often fall because of poor muscle strength and reduced balancing ability related to muscle aging. However, it is unclear whether changes in muscle fiber types contribute to poor strength or imbalance. We studied age- associated changes in human skeletal muscle fibers using muscle biopsy specimens taken from 65 male and female Chinese patients aged 17-96 years. The muscle specimens were cryosectioned with alkaline triphosphatase staining at pH 4.4, followed by image analysis. We analyzed morphologic observations and performed quantitative analyses of the number, size, and area percentage of different types of skeletal muscle fibers and connective tissues. Types IIA and IIB muscle fibers decreased with age in the area percentage, fiber number percentage, and mean fiber area, whereas Type I fibers increased in area and number but not in size. Morphologically, Type II fibers appeared smaller and flatter. Our findings suggest deterioration in muscle quality and balancing coordination in elderly patients. We provide data to help determine treatments for reversing muscle fiber changes and reducing the number of falls and related fractures in patients.

Ultrastructure and innervation of regenerated intrafusal muscle fibres in heterochronous isografts of the fast rat muscle.

Extensor digitorum longus (EDL) muscles from 2- to 28-day-old rats were grafted into EDL muscles of adult inbred recipients (n = 8). At 1-6 months after the operation, experimental muscles were excised and the ultrastructure and innervation of regenerated muscle spindles was examined. Regenerated muscle spindles (n = 36) in isografted EDL muscles contained 4.3 +/- 0.2 (mean +/- SEM) encapsulated muscle fibres. These "intrafusal" muscle fibres lacked nuclear bag and nuclear chain accumulations, which are characteristic of normal muscle spindles; thus, they rather resembled thin encapsulated extrafusal muscle fibres. In the same sample, myelinated axons were found in 33 (92%) muscle spindles, but no sensory terminals were found. These findings demonstrate that regenerated spindles in isografted EDL muscles were not reinnervated by spindle-specific sensory axons, but exclusively by motor axons. Typical intracapsular motor endplates (MEPs) were found in one third of regenerated spindles examined. Their motor terminals contained accumulated mitochondria and synaptic vesicles. As is characteristic for MEPs, axolemma and sarcolemma were separated by a synaptic cleft about 60 nm wide that contained a basal lamina. The underlying sarcolemma formed either small infoldings or none at all, and the subsynaptic area contained only small subsarcolemmal accumulations of mitochondria. It is apparent that the structures described here as "regenerated muscle spindles" do not perform their normal physiological function as stretch receptors because they lack the sensory innervation. The present results show that regeneration and reinnervation in heterochronous isografts corresponds to that previously described in autotransplanted free muscle grafts. The results also show that, during muscle spindle regeneration, intrafusal satellite cells develop into extrafusal-like muscle fibres, apparently due to their motor innervation.

Regenerated rat fast muscle transplanted to the slow muscle bed and innervated by the slow nerve, exhibits an identical myosin heavy chain repertoire to that of the slow muscle.

The hypothesis that the limited adaptive range observed in fast rat muscles in regard to expression of the slow myosin is due to intrinsic properties of their myogenic stem cells was tested by examining myosin heavy chain (MHC) expression in regenerated rat extensor digitorum longus (EDL) and soleus (SOL) muscles. The muscles were injured by bupivacaine, transplanted to the SOL muscle bed and innervated by the SOL nerve. Three months later, muscle fibre types were determined. MHC expression in muscle fibres was demonstrated immunohistochemically and analysed by SDS-glycerol gel electrophoresis. Regenerated EDL transplants became very similar to the control SOL muscles and indistinguishable from the SOL transplants. Slow type 1 fibres predominated and the slow MHC-1 isoform was present in more than 90% of all muscle fibres. It contributed more than 80% of total MHC content in the EDL transplants. About 7% of fibres exhibited MHC-2a and about 7% of fibres coexpressed MHC-1 and MHC-2a. MHC-2x/d contributed about 5-10% of the whole MHCs in regenerated EDL and SOL transplants. The restricted adaptive range of adult rat EDL muscle in regard to the synthesis of MHC-1 is not rooted in muscle progenitor cells; it is probably due to an irreversible maturation-related change switching off the gene for the slow MHC isoform.